Inteins (internal proteins) are genetic elements similar to self-splicing introns; however, inteins are transcribed and translated together with their host protein. Only at the protein level do the inteins excise themselves from the host protein. Organism from all three domain of life contains intein; Archea, Eubacteria and Eukarya, they have been found in yeast and algal chloroplasts, mycobacteria, cynobacteria, and in thermophilic archaea. The two portions of the host protein separated by the intein are called exteins (external proteins). During the splicing process the intein is excised, the two exteins are joined by a peptide bond, and the host protein assumes its normal folding and function. The first intein was discovered in 1987 when the carrot and Neurospora crassa vacuolar ATPases were compared with a putative Ca2C pumpingATPase. The latter had been isolated as a gene whose mutation made yeast resistant against the calmodulin antagonist trifluoperazine. The beginning and end of the encoded protein was very similar to the vacuolar ATPase subunits whose sequences had been submitted to the databanks at the same time. However, the central region of the putative calcium pump had no similarity to any known ATPase. Rather, this portion showed weak similarity to endonucleases. Anraku's lab. isolated the cDNA for the yeast vacuolar ATPase A-subunit and found the same sequence, including the central region, that had been earlier described as the trifluoperazine resistance gene. Surprisingly, denaturing polyacrylamide gel electrophoresis of the isolated protein demonstrated that the catalytic subunit of the functioning yeast V-ATPase had a molecular weight of only 70 kDa, as expected for a subunit without the insertion. Subsequently showed that the insertion was still present in the mRNA, that the whole protein including the insertion was translated, and that the insertion spliced itself out of the protein during posttranslational processing.

No essential role has been shown for inteins. All their identified function involved their own preservation and maintenance, with no apparent benefit to the host protein and organism. At least some inteins are multifunctional, being able to both catalyze their own protein splicing and to home a copy of their gene into intein-less alleles. The protein splicing function can be further divided in to cleavage of intein N-terminal end and ligation of the two host flanks (exteins) followed by cleavage of the intein C- terminal end.